At the present time, patients with diabetes rely on self-monitoring of blood glucose, using an invasive blood glucose meter several times every day. This method typically involves drawing a small sample of blood, which is then tested directly for glucose level. There are numerous drawbacks to this method. The patient must draw samples of blood every day, several times a day at regular intervals. There is some discomfort associated with drawing blood samples repeatedly. Also, there is a margin for error. For example, patients may forget to take blood samples when required. It would be of great economical as well as medical interest to develop a new device for self-monitoring of blood glucose that facilitates continuous monitoring of blood glucose level, that is reliable and accurate, but does not negatively impact a patient's quality of life. Health costs would be lowered and the quality of life for diabetes patients would be greatly improved.
There have been attempts at developing non-invasive glucose measurement techniques that are able to monitor blood glucose concentration. Non-invasive measurement systems could minimize the discomfort to patients and also provide more accurate, risk-free measurement of glucose and the required dosage of insulin. By non-invasive techniques, it will be understood that the surface of the skin is not broken and/or samples of body tissues, including bodily fluids such as blood, from patients is not required.
Some of these methods involve measurement of impedance of certain types of electromagnetic radiation with or through body tissues. This is also known as bioimpedance. Impedance measurements have been used previously to evaluate different types of body conditions. As the total impedance of body tissue depends on a variety of factors, including cellular structure and the composition of both extra and intra cellular fluid, it can be a good diagnostic tool in health care. Body tissue impedance has used in a number of other applications, including estimation of skin irritation from different chemicals (Nicander, I. (1998) “Electrical impedance related to experimentally induced changes of human skin and oral mucosa” PhD thesis, Karolinska Institutet), cardiac monitoring function (Min, M. et al. “Electrical Impedance and Cardiac Monitoring—Technology, Potential and Applications.” International Journal of Bioelectromagnetism, v. 5: 53-56, 2003), and skin cancer detection (Beetner D. G., et al. (2003): “Differentiation among basal cell carcinoma, benign lesions, and normal skin using electric impedance”, IEEE T Bio-Med Eng, 50(8), pp 1020-1025; Aberg P. et al. (2003) “Minimally invasive electrical impedance spectroscopy of skin exemplified by skin cancer assessments”, Proc IEEE EMBS, Cancun (MX), 17-21 Sep. 2003, pp 3211-3214, ISBN 07803-7790-7).
Non-invasive methods for determining blood glucose level, involving measurement of skin tissue impedance have been described. For example, U.S. Pat. No. 5,036,861 (issued to Sembrowich et al. on Aug. 6, 1991) describes a wrist-mountable device having an electrode which measures glucose present in sweat at the skin surface. WO 01/26538 (to Sηsstrunk, et al, published Oct. 13, 2000) describes another wrist-mountable device for measurement of blood glucose. U.S. Pat. No. 5,222,496 (issued to Clarke et al. on Jun. 29, 1993) describes an infrared glucose sensor mountable, for instance, on a wrist or finger. U.S. Pat. No. 5,433,197 (issued to Stark on Jul. 18, 1995) describes determination of blood glucose through illuminating a patient's eye with near-infrared radiation. U.S. Pat. Nos. 5,115,133, 5,146,091 and 5,197,951 (issued to Knudson on May 19, 1992, Sep. 8, 1992 and Jan. 19, 1993, respectively) describe measuring blood glucose within blood vessels of a tympanic membrane in a human ear through light absorption measurements. WO 9504496 (to Fuller, published Feb. 16, 1995, describes the use of radio frequency spectroscopy to determine concentrations of blood analytes, including glucose. WO98/04190 (to Elden et al., published Feb. 5, 1998) and WO99/39627 (to Elden et al., published Aug. 12, 1999) describe the use of measuring skin tissue impedance to determine glucose concentration in a body fluid. EP Application No. 1 437 091, to Ollmar et al., published on Jul. 14, 2004 describes a minimally invasive method and apparatus for measuring skin impedance and correlation with blood glucose level, by way of an electrode with micromachined spikes which penetrate the skin surface. Finally, U.S. Pat. No. 5,353,802 (issued to Ollmar on Oct. 11, 1994) describes a probe with a plurality of electrodes for detection and characterization of surface phenomena in a body tissue, by surface measurement of the impedance of the tissue. The specifications of the references cited above are incorporated herein by reference.
There may be difficulties associated with the correlation of skin impedance to glucose levels or concentrations in body fluids. For example, the accuracy and reproducibility of skin impedance measurements can be affected by several factors, including the condition of the skin, which may vary between individuals. Such conditions can include, for example, the thickness of the skin, the location on the body where the impedance measurement is taken, the presence of dirt and/or oils on the surface and/or the presence of inflammation or a disease state affecting the skin. The accuracy and reproducibility of skin impedance measurements is also affected by the nature of skin tissue. These difficulties may not be overcome with some prior art devices or methods.
Accordingly, there is a need for a more accurate and reproducible method to allow monitoring of body fluid glucose levels, such as blood glucose levels.